Karen Sfanos and Angelo De Marzo: Inflammation may play a role
in cancer caused by PhIP.
Several years ago, scientist Bill Nelson, M.D., Ph.D., now director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, introduced the readers of this publication to a funny little word: "PhIP." It sounds so harmless, but PhIP, an abbreviation for a long chemical name, is something known as a pro-carcinogen. Not necessarily bad in itself, it can be metabolized to something more dangerous: a chemical that attacks and mutates DNA and is known to cause prostate, colon, and breast cancer in rats.
Unfortunately for those of us who love charred meat, we create carcinogens, or cancer-causing agents, with every steak, hamburger, or piece of chicken we grill or fry – and PhIP is one of them. In 2007, Nelson and pathologist Angelo De Marzo, M.D., Ph.D., reported in Cancer Research that when rats are exposed to PhIP, DNA mutations occur in the prostate. Recently, Karen Sfanos, Ph.D., who was a postdoctoral fellow in De Marzo's lab and since has joined the faculty, has added striking new findings to our knowledge of PhIP. Her work brings together not only the groundbreaking studies by Nelson and De Marzo of the role of diet in prostate cancer, but the pioneering ideas being carried out by Nelson, De Marzo, William Isaacs, The Dr. and Mrs. Peter S. Bing Scholar, Elizabeth Platz, The Martin D. Abeloff, M.D. Scholar in Cancer Prevention and others at the Brady involving inflammation and the start of prostate cancer.
In rats, Sfanos has found that if the prostate becomes infected at a time when the diet also includes PhIP, this "combination of environmental insults" can encourage the development of prostate cancer. The rat prostate is a small gland, but it has different areas, or lobes, that are made up of different types of tissue. In the PhIP-treated rats, prostate cancer develops only in the ventral lobe. In men, cancer occurs mainly in what's called the peripheral zone of the prostate. "De Marzo's group found that after exposure to PhIP, there was also an increase in stromal mast cells and macrophages – inflammatory cells that play a key role in immune defenses – only in the ventral lobe of the rat prostate," says Sfanos. "This finding, that infiltration of inflammatory cells was restricted to the very same lobe of the prostate that developed cancer, suggests that inflammation may play a role in cancer caused by PhIP."
Unfortunately for those of us
who love charred meat, we create carcinogens,
or cancercausing agents, with every steak, hamburger,
or piece of chicken we grill or fry –
and PhIP is one of them.
To explore the association between inflammation in the prostate, PhIP and cancer, Sfanos and colleagues decided to see whether chronic inflammation caused by bacterial infection could make a difference in rats that had consumed PhIP. She used a specific strain of E.coli that was isolated from a patient with chronic prostatitis/chronic pelvic pain syndrome by Anthony Schaeffer, M.D., of Northwestern University, and further studied by Brady urologist Edward Schaeffer, M.D., Ph.D. "What we unexpectedly found was that the E. coli infection in the prostate and inflammation in the PhIPtreated rats appeared to have a systemic effect," says Sfanos. "This led to an increase in the development and progression of cancer in multiple sites, including the skin and the gastrointestinal tract."
Even more remarkable was that the rats that received the "double whammy" of E. coli and PhIP fared worse than rats that received PhIP alone. "The animals that received both PhIP and E. coli developed more precancerous lesions on average within the prostate compared to the animals that had PhIP alone," says Sfanos. This difference in the development of precancerous lesions within the prostate may have been even more pronounced, she adds – except animals treated with PhIP plus E.coli died sooner. They "exhibited a marked decrease in median survival due to a twofold increase in the development of invasive cancers at other sites. This phenomenon of an increase in the development and progression of cancer at multiple sites may have been mediated in part by an elevated level of cytokines in the blood of the animals caused by the infection." (For more on cytokines, see story.) Sfanos believes that this rat model may be helpful in future studies of the bad combination of diet and infection in the development of prostate and other forms of cancer.
Also taking part in this study were Kirstie Canene-Adams, Brian Simons, William Nelson, and Charles Drake.